WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF is characterized by epithelial cell injury and reprogramming, increases in (myo)fibroblasts, and altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) is involved in impaired epithelial-mesenchymal crosstalk in pulmonary fibrosis. Here, we aimed to further investigate WISP1 regulation and function in primary human lung fibroblasts (phLFs). We demonstrate that WISP1 is directly upregulated by Transforming growth factor ß1 (TGFß1) and Tumor necrosis factor α (TNFα) in phLFs, using a luciferase-based reporter system. WISP1 mRNA and protein secretion increased in a time- and concentration-dependent manner by TGFß1 and TNFα in phLFs, as analysed by qPCR and ELISA, respectively. Notably, WISP1 is required for TGFß1- and TNFα-dependent induction of interleukin 6 (IL-6), a mechanism that is conserved in IPF phLFs. The siRNA-mediated WISP1 knockdown led to a significant IL-6 reduction after TGFß1 or TNFα stimulation. Furthermore, siRNA-mediated downregulation or antibody-mediated neutralization of WISP1 reduced phLFs proliferation, a process that was in part rescued by IL-6. Taken together, these results strongly indicate that WISP1-induced IL-6 expression contributes to the pro-proliferative effect on fibroblasts, which is likely orchestrated by a variety of profibrotic mediators, including Wnts, TGFß1 and TNFα.

Incidence of Salmonella in fish and seafood.

Field laboratories of the U.S. Food and Drug Administration collected and tested 11,312 import and 768 domestic seafood samples over a 9-year period (1990 to 1998) for the presence of Salmonella. The overall incidence of Salmonella was 7.2% for import and 1.3% for domestic seafood. Nearly 10% of import and 2.8% of domestic raw seafood were positive for Salmonella. The overall incidence of Salmonella in ready-to-eat seafood and shellfish eaten raw was 0.47% for domestic--one shucked oyster and one shark cartilage powder. The incidence in the 2,734 ready-to-eat import seafood was 2.6%--cooked shrimp, shellfish or fish paste, smoked fish, salted/dried fish, and caviar. The incidence in import shellfish consumed raw was 1% in oyster, 3.4% in clams, and 0% in mussels. The incidence in raw, import fish was 12.2%. Distribution of Salmonella in seafood on a regional basis indicated the incidence to be highest in central Pacific and Africa and lowest in Europe/Russia and North America (12% versus 1.6%). Data on a country basis indicated Vietnam to have the highest (30%) and Republic of Korea the lowest (0.7%). While the most frequent serotypes in import seafood were Salmonella Weltevreden (1st), Salmonella Senftenberg (2nd), Salmonella Lexington, and Salmonella Paratyphi-B (3rd, equal numbers for each serotype), the top 20 list included Salmonella enteritidis (5th), Salmonella Newport (6th), Salmonella Thompson (7th), Salmonella typhimurium (12th), and Salmonella anatum (13th), commonly involved in foodborne illness in the United States. Because the incidence in the present study is based on only a small fraction of the seafood imported into the United States, efforts should be directed toward implementation of hazard analysis and critical control points to reduce the incidence of Salmonella in seafood without relying on testing for Salmonella.

Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin.

INTRODUCTION: During the 1970s, scientists suggested that the growing use of chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric ozone layer with potentially harmful results. A committee on the ozone layer organized the preparation of the Montreal Protocol. This protocol mandated the cessation of production and use of CFCs by January 1, 1996. The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs) for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a selective beta-adrenergic agonist, currently widely available for inhalation asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction. METHODS: This was a randomized, single-blind, placebo-controlled, 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction. Twenty patients self administered two puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to performing a standardized exercise challenge at the study site. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes after completion of the exercise challenge. Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval. RESULTS: The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise. The smallest percent change from predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20% FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil respectively. Changes in heart rate, blood pressure and QT corrected interval were similar for the three active treatments following exercise. CONCLUSIONS: Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo. Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction.

Epidemiologic evaluation of encephalitic listeriosis in goats.

OBJECTIVE: To evaluate host and environmental factors associated with the development of encephalitic listeriosis in goats. DESIGN: Retrospective analysis of diagnostic laboratory records and survey of veterinarians and goat producers. SAMPLE POPULATION: 355 goat herds accessible through laboratory records; 38 veterinarians who treated goats and 76 goat producers. PROCEDURE: Data regarding breed and use for goats affected with encephalitic listeriosis were obtained from surveys and case follow-up information. Listeria monocytogenes isolates from the brains of 7 affected goats were serotyped and subjected to DNA restriction analysis. RESULTS: Odds ratio for the development of encephalitis listeriosis in Angora (mohair-producing) goats was 22.9 by use of diagnostic laboratory records. Survey also revealed a high prevalence in herds of Angora and other breeds that subsisted on woody browse, although Angora goats feeding predominantly on hay or pasture were not affected. Listeria monocytogenes isolates from 4 Angora goats in 3 herds differed in DNA restriction patterns, although the pattern was identical in 3 other goats from another herd. CLINICAL IMPLICATIONS: Encephalitic listeriosis can be observed in all goat breeds, but a lifestyle of heavy browse consumption seems important to the development of disease in some herds.

Efficacy of once daily extended-release theophylline in decreasing the use of inhaled beta 2-agonists in stable, mild-to-moderate asthma patients.

BACKGROUND/OBJECTIVE: The purpose of this study was to determine whether the addition of extended-release theophylline to the daily treatment regimen of inhaled beta 2-agonist users would result in decreased use of beta 2-agonist while maintaining similar efficacy for treatment of asthma. METHODS: This was a single-blind, multicenter (six sites) study. Sixty-one patients with a history of mild-to-moderate asthma treated with inhaled beta 2-agonist were randomized to treatment with Theo-24 (anhydrous extended-release capsules) plus inhaled beta 2-agonist or placebo plus beta 2-agonist. Patients kept daily symptom diaries, measured peak flow rates, recorded puffs of inhaled beta 2-agonist, and adverse events during a 4-week treatment period. RESULTS: Fifty-five patients were included in the efficacy analysis. The primary efficacy variable in this study was the mean number of puffs (adjusted for baseline differences) of beta 2-agonist inhaled per day. In this study, the addition of theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo. The differences were significant at the P < .05 level. For patients in the theophylline group, the number of puffs decreased from an unadjusted mean of 9.81 at baseline to an adjusted mean of 6.78 after 4 weeks of treatment compared with 9.91 at baseline and 8.17 for the placebo group. There were no unexpected or serious adverse events. CONCLUSIONS: In this study, the addition of once daily, extended-release theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo, while maintaining acceptable asthma symptom scores.

Health Care Plan's Nurse Advice System.

Staff model HMO's expend great effort in handling member phone calls. Health Care Plan, Inc. has developed a computer program to aid phone room nurses in their documentation and decision making processes. The Nurse Advice system has been successfully implemented in six of eight medical centers. By providing real-time access to patient clinical data, the quality of care and service is improved.

The pros and cons of a mass-media colorectal screening program.

Saint John's Hospital Cancer Center attempted an extensive colorectal screening project encompassing some 34,000 square miles with a population of 13,000,000. Even though our response was encouraging, it still fell far short of expected participants. We found the media played an invaluable role; for as the television coverage diminished, so did the number of kits returned for processing. We wonder if, perhaps, we spread ourselves "too thin." Perhaps the screening program should be more regionally based among community hospitals? Should our targeting be re-directed; ie., towards retirement communities and homes? Is the use of colorectal screening kits truly a cost-effective method of healthcare delivery? These questions can only be answered through further participation of community cancer centers nationally. It is our hope that through continued testing, screening programs will become more refined and productive, ensuring the highest standards of medical care provided to our communities.

Listeria spp. found on fresh market produce.

From October 1987 to August 1988, 1,000 tests were conducted on 10 types of fresh produce from two Minneapolis area supermarkets to detect Listeria spp. The produce included broccoli, cabbage, carrots, cauliflower, cucumbers, lettuce, mushrooms, potatoes, radishes, and tomatoes. The vegetables were tested by the Food and Drug Administration method for isolation of Listeria spp., with the addition of LiCl-phenylethanol-moxalactam agar in the last 280 tests; 8.6 and 11.4% of these tests were positive by modified McBride and LiCl-phenylethanol-moxalactam agars, respectively. Listeria monocytogenes was isolated from cabbage, cucumbers, potatoes, and radishes; L. innocua was isolated from cucumbers, lettuce, mushrooms, potatoes, and radishes; L. seeligeri was isolated from cabbage and radishes; and L. welshimeri was isolated from cucumbers, potatoes, and radishes. The isolates were of various serotypes; however, the L. monocytogenes isolates were predominantly serotype 1 (82%). Only potatoes (25.8% positive) and radishes (30.3% positive) showed significant amounts of L. monocytogenes contamination.

Primary melanoma: pitfalls in diagnostic biopsy techniques and interpretations.

A group of 235 patients with melanoma were followed for 10 years. In 25 of these patients, the initial biopsy specimen obtained by the shave, punch, or incisional technique was insufficient to determine the microscopic extent of the lesion. Guidelines for treatment of these patients include evaluation of the deepest level of tumor invasion, a clinical history of the lesion, and a careful physical examination. If any visible melanoma remains, total excisional rebiopsy should be performed before definitive treatment is begun. Of the 25 patients thus managed, recurrences developed in 3 within 2 years of initial treatment. In two patients, reexcisional surgery was carried out, and they are currently free of disease. One patient died from systemic metastases. Total excisional biopsy of lesions suspected of being melanomas is strongly recommended, and shave, punch, or incisional techniques should be avoided.

Carcinoma of the pancreas: progress or stalemate?

Has treatment for cancer of the pancreas progressed or has a stalemate been reached? This is a difficult question to answer. Cancer of the pancreas has several unique features. First, it has been an extremely difficult tumor to study because of its anatomic location and our present invasive and non-invasive studies have failed to provide for truly early detection of this disease when cure may be possible. Second, assuming that we are able to diagnose early, radical surgical resection (our best treatment to date) still carries a substantial morbidity and mortality. The direction certainly has to be in early detection and screening in the asymptomatic patient. To date all of our therapy is directed to the patient who already has symptoms. Diagnosis prior to this stage of the disease is imperative. This would entail the use of biological and serum antibody-type screening procedures with specific tumor markers and better epidemiologic studies to identify risk factors which would aid in screening procedures. It is apparent that present day techniques in the diagnosis and directions are needed before any significant improvement in survival rates are realized.

ICMSF Methods Studies. XIV. Comparative Study on Recovery of Salmonella from Refrigerated Preenrichment and Enrichment Broth Cultures.

Twelve laboratories from 7 countries compared the productivity of refrigerated (72 h at 5 to 10°C) preenrichment and enrichment broth cultures with a standard cultural procedure for detection of Salmonella in 466 naturally contaminated low and high moisture foods. Refrigerated preenrichment and enrichment cultures identified 92.5 and 94.2% of contaminated samples, respectively. Variations in the ability of laboratories to successfully recover salmonellae under refrigeration test conditions were notable. Three laboratories found complete agreement between results by the standard and refrigeration test procedures and 5 additional laboratories reported >90% accuracy; lowest recovery rate for combined refrigeration results was 77%. Sensitivity of the refrigeration techniques was markedly greater with low than high moisture foods where the latter contributed all but two of the 62 false-negative results encountered in this study. Ability of individual laboratories to recover Salmonella from refrigerated preenrichment and enrichment broth cultures was not significantly different for given food categories. Productivity of paired enrichment-plating media differed widely with food type. Selective enrichment in tetrathionate brilliant green and plating on bismuth sulfite agar showed greatest sensitivity for isolation of Salmonella in high but not in low moisture foods where productivity of the 4 enrichment-plating conditions used in this study was comparable. Results on recoverability of Salmonella from refrigerated broth cultures concur with findings of an earlier comparative study and strongly support incorporation of this novel approach in standard cultural methods for detection of Salmonella in foods.

Incidence of salmonellae in fecal samples of production swine and swine at slaughter plants in the United States in 1978.

Nine swine slaughter plants and 19 swine production units were randomly selected for sampling from the six highest swine-producing states representing a total of 64% of the United States swine production. Three composites of 10 fresh swine fecal samples were obtained from each slaughter plant, representing three different farm sources of swine. Two composite fecal samples were collected from two different production pens from each production unit. Samples were analyzed for salmonellae. Isolated salmonellae were biochemically and serologically identified and tested for antibiotic susceptibility and resistance transfer ability. Salmonellae were recovered from swine at seven of the nine slaughter plants and 16 of the 27 composites of slaughter swine. Of the 19 production units, 3 had swine shedding salmonellae. Resistances found included streptomycin, tetracycline, and sulfadiazine. Of the 52 total isolates tested, 71% had some level of antibiotic resistance. Only 3 of 37 resistant isolated could transfer resistance under the conditions used.

A retrospective study of regional perfusion for melanoma.

Regional perfusion has been utilized in the treatment of accessible melanomas for many years. This series of 245 patients, which encompasses over ten years of experience, is presented to reevaluate the results of regional perfusions in melanomas, and perhaps to redefine the indications for such a procedure. Fifty-nine patients died from three months to over five years following the procedure, and six of the deaths were from diseases other than melanoma. The overall survival in stage I disease was 93%; stage II, 68%; and stage III, 41%. There were no survivors in stage IV. Nearly all of the recurrences and deaths from disease were seen within two years of the perfusion. These results are similar to others, and 10% to 15% better than those of conventional methods. Indications are now more definite, and include most invasive melanomas in an area accessible to perfusion technique, except in very elderly and poor risk patients, those with severe arteriosclerosis in the area concerned, and those with widespread metastases.

An evaluation of bilateral breast carcinoma. Simultaneous and sequential lesions.

The detection of bilateral breast carcinoma, simultaneous or nonsimultaneous, appears to be increasing. Undoubtedly a major factor in this is the increased use of mammography and xeromammography. In a 21-year period at Saint John's Hospital and Health Center, 1,189 cases of primary breast carcinoma were treated, of which 34 (2.9 percent) were bilateral. However, from 1972 to 1974 the incidence has risen from 1.9 to 10.8 percent, with a simultaneous rise in numbers of xeromammograms made. Xeromammography should be done routinely in patients in whom carcinoma of the breast is suspected. Its use should also be an integral part of the follow-up in patients in whom mastectomy has been carried out previously.